Heliette Chapuis

A specific function for phosphatidylinositol 3-kinase α (p85α-p110α) in cell survival and for phosphatidylinositol 3-kinase β (p85α-p110β) in de novo DNA synthesis of human colon carcinoma cells

We have previously shown an important function of phosphatidylinositol 3-kinase (PI3K)α(p85α-p110α) and PI3Kβ (p85-α-p110β) for DNA synthesis induced by various mitogens in non transformed fibroblasts and we now report a specific role of these enzymes in human colon cancer cell growth. Using antibodies specific to p110α and to p110β catalytic subunits, increase in PI3Kα and PI3Kβ activities was detected in 15/19 human tumour biopsies relative to adjacent normal mucosa of human colon and bladder. Increase in such activities was also observed in adenocarcinoma cell lines CaCo2, CO115, HCT 116, LS 174T and WiDr relative to non-transformed fibroblasts. Maximal PI3Kα activity was observed for LS 174T and PI3Kβ activity for WiDr cells. This was partly correlated with an increase in p110α and p110β protein levels both in some primary tumours and established cell lines, suggesting that PI3K overexpression is involved in enzymatic deregulation. Functional consequence of such activation was assessed by a microinjection approach. An injection of neutralizing antibody specific to p110β in WiDr, HCT116 and CO 115 cells inhibited de novo DNA synthesis, whereas antibodies specific to p110γ had no effect. Neutralizing antibodies specific to p110α induced apoptosis, a response that was reverted by treating cells with the caspase inhibitor z-VAD-fmk. However anti-p110β and anti-p110γ antibodies did not affect cell survival. We concluded that PI3Kα and PI3Kβ play important roles in human colon cancer cell growth with a specific function for PI3Kβ in de novo DNA synthesis and an involvement of PI3Kα in cell survival.

The Use of Preoperative Routine Measurement of Basal Serum Thyrocalcitonin in Candidates for Thyroidectomy due to Nodular Thyroid Disorders: Results from 2733 Consecutive Patients

CONTEXT The preoperative routine measurement of basal serum thyrocalcitonin (CT) in candidates for thyroidectomy due to thyroid nodules is currently a subject of debate. OBJECTIVE The objective of this study was to evaluate the role of systematic basal serum CT measurement in improving the diagnosis and surgical treatment of medullary thyroid carcinoma (MTC) in patients undergoing thyroidectomy for nodular thyroid disorders, regardless of preoperative CT levels. DESIGN We determined basal serum CT levels in 2733 consecutive patients before thyroid surgery and performed a pentagastrin test in patients with hypercalcitoninemia. We correlated basal and stimulated CT levels with intraoperative and definitive histopathological findings, and we analyzed the impact of these results on surgical procedures. RESULTS Twelve MTCs were found among the 43 patients with basal serum CT level of 10 pg/ml or greater. Two MTCs were present among the 2690 patients with normal CT levels. MTC was always present in patients with a basal CT of 60 pg/ml or greater. For CT levels ranging from 10 to 59 pg/ml, MTC was diagnosed in 11% of patients. When preoperative hypercalcitoninemia was present, total thyroidectomy associated with comprehensive intraoperative histopathological analysis allowed the intraoperative diagnosis of five latent, subclinical MTCs. The pentagastrin test gave no additional diagnostic information for the management of patients with elevated preoperative basal serum CT level. CONCLUSION Routine measurement of CT in the preoperative work-up of nodular thyroid disorders is useful. This procedure improves intraoperative diagnosis of MTC and enables adapted initial surgery, the most determinant factor of treatment success.

Clinical relevance of nine transcriptional molecular markers for the diagnosis of head and neck squamous cell carcinoma in tissue and saliva rinse

BackgroundAnalysis of 23 published transcriptome studies allowed us to identify nine genes displaying frequent alterations in HNSCC (FN1, MMP1, PLAU, SPARC, IL1RN, KRT4, KRT13, MAL, and TGM3). We aimed to independently confirm these dysregulations and to identify potential relationships with clinical data for diagnostic, staging and prognostic purposes either at the tissue level or in saliva rinse.MethodsFor a period of two years, we systematically collected tumor tissue, normal matched mucosa and saliva of patients diagnosed with primary untreated HNSCC. Expression levels of the nine genes of interest were measured by RT-qPCR in tumor and healthy matched mucosa from 46 patients. MMP1 expression level was measured by RT-qPCR in the salivary rinse of 51 HNSCC patients and 18 control cases.ResultsDysregulation of the nine genes was confirmed by the Wilcoxon test. IL1RN, MAL and MMP1 were the most efficient diagnostic markers of HNSCC, with ROC AUC > 0.95 and both sensitivity and specificity above 91%. No clinically relevant correlation was found between gene expression level in tumor and T stage, N stage, tumor grade, global survival or disease-free survival. Our preliminary results suggests that with 100% specificity, MMP1 detection in saliva rinse is potentially useful for non invasive diagnosis of HNSCC of the oral cavity or oropharynx, but technical improvement is needed since sensitivity was only 20%.ConclusionIL1RN, MAL and MMP1 are prospective tumor diagnostic markers for HNSCC. MMP1 overexpression is the most promising marker, and its detection could help identify tumor cells in tissue or saliva.

Reference gene selection for head and neck squamous cell carcinoma gene expression studies

BackgroundIt is no longer adequate to choose reference genes blindly. We present the first study that defines the suitability of 12 reference genes commonly used in cancer studies (ACT, ALAS, B2M, GAPDH, HMBS, HPRT, KALPHA, RPS18, RPL27, RPS29, SHAD and TBP) for the normalization of quantitative expression data in the field of head and neck squamous cell carcinoma (HNSCC).ResultsRaw expression levels were measured by RT-qPCR in HNSCC and normal matched mucosa of 46 patients. We analyzed the expression stability using geNorm and NormFinder and compared the expression levels between subgroups. In HNSCC and/or normal mucosa, the four best normalization genes were ALAS, GAPDH, RPS18 and SHAD and the most stable combination of two genes was GAPDH-SHAD. We recommend using KALPHA-TBP for the study of T1-T2 tumors, RPL27-SHAD for T3-T4 tumors, KALPHA-SHAD for N0 tumors, and ALAS-TBP for N+ tumors. ACT, B2M, GAPDH, HMBS, HPRT, KALPHA, RPS18, RPS29, SHAD and TBP were slightly misregulated (<1.7-fold) between tumor and normal mucosa but can be used for normalization, depending on the resolution required for the assay.ConclusionIn the field of HNSCC, this study will guide researchers in selecting the most appropriate reference genes from among 12 potentially suitable reference genes, depending on the specific setting of their experiments.

Transoral robotic surgery for the treatment of T1–T2 carcinoma of the larynx: Preliminary study

To determine the feasibility and the preliminary oncological results of transoral robotic surgery (TORS) for the treatment of early stage laryngeal tumors.

Metachronous renal oncocytomatosis.

A renal oncocytoma is a benign and usually solitary lesion. We present a new case of diffuse oncocytomatosis in one kidney after previous contralateral surgery for an isolated oncocytoma. This very unusual situation must be kept in mind in cases of multifocal oncocytomas, as a recurrence will generally occur after partial surgery.

Updated definition of level VI lymph node classification in the neck

Conclusion. This update will enable us to precisely address the involvement pattern of level VI and to standardize treatment procedures in order to refine their indications and eventually improve their results and avoid treatment morbidity. Background. The neck level classification is being used worldwide to describe the lymph nodes status of the neck. It provides standardized data to properly evaluate and then improve our protocols for the management of neck metastasis in an evidence-based medical manner. Although level VI treatment is challenging in cancer of the larynx, pharynx, trachea, esophagus, and thyroid, our knowledge about its involvement relies on few non-standardized data, due to the inadequate definition of this region. Method. We propose an updated radiological and surgical definition of level VI, with the introduction of two sublevels which fulfill surgical, radiotherapy, radiological, and pathological concerns. Results. Level VIa encompasses prelaryngeal, intercricothyroidal, pretracheal, and perithyroidal nodes. Level VIb encompasses inferior laryngeal nodes. Within the traditional limits of level VI, all lymph nodes lying between the inferior border of the hyoid bone and the inferior border of the cricoid cartilage belong to level VIa. Between the inferior border of the cricoid cartilage and the top of the suprasternal notch, lymph nodes lying in front of the posterior face of the thyroid gland belong to level VIa; those lying behind this boundary belong to level VIb. We also discuss the definition of the superior mediastinal lymph nodes, which should not be mistaken for level VI.